Improving gene annotation using peptide mass spectrometry

Annotation of protein-coding genes is a key goal of genome sequencing projects. In spite of tremendous recent advances in computational gene finding, comprehensive annotation remains a challenge. Peptide mass spectrometry is a powerful tool for researching the dynamic proteome and suggests an attractive approach to discover and validate protein-coding genes. We present algorithms to construct and efficiently search spectra against a genomic database, with no prior knowledge of encoded proteins. By searching a corpus of 18.5 million tandem mass spectra (MS/MS) from human proteomic samples, we validate 39,000 exons and 11,000 introns at the level of translation. We present translation-level evidence for novel or extended exons in 16 genes, confirm translation of 224 hypothetical proteins, and discover or confirm over 40 alternative splicing events. Polymorphisms are efficiently encoded in our database, allowing us to observe variant alleles for 308 coding SNPs. Finally, we demonstrate the use of mass spectrometry to improve automated gene prediction, adding 800 correct exons to our predictions using a simple rescoring strategy. Our results demonstrate that proteomic profiling should play a role in any genome sequencing project.

SelenoDB 1.0 : a database of selenoprotein genes, proteins and SECIS elements

Selenoproteins are a diverse group of proteinsusually misidentified and misannotated in sequencedatabases. The presence of an in-frame UGA (stop)codon in the coding sequence of selenoproteingenes precludes their identification and correctannotation. The in-frame UGA codons are recodedto cotranslationally incorporate selenocysteine,a rare selenium-containing amino acid. The developmentof ad hoc experimental and, more recently,computational approaches have allowed the efficientidentification and characterization of theselenoproteomes of a growing number of species.Today, dozens of selenoprotein families have beendescribed and more are being discovered in recentlysequenced species, but the correct genomic annotationis not available for the majority of thesegenes. SelenoDB is a long-term project that aims toprovide, through the collaborative effort of experimentaland computational researchers, automaticand manually curated annotations of selenoproteingenes, proteins and SECIS elements. Version 1.0 ofthe database includes an initial set of eukaryoticgenomic annotations, with special emphasis on thehuman selenoproteome, for immediate inspectionby selenium researchers or incorporation into moregeneral databases. SelenoDB is freely available athttp://www.selenodb.org.

OSIRISv1.2: a named entity recognition system for sequence variants of genes in biomedical literature

Background: Single Nucleotide Polymorphisms, among other type of sequence variants, constitute key elements in genetic epidemiology and pharmacogenomics. While sequence data about genetic variation is found at databases such as dbSNP, clues about the functional and phenotypic consequences of the variations are generally found in biomedical literature. The identification of the relevant documents and the extraction of the information from them are hampered by the large size of literature databases and the lack of widely accepted standard notation for biomedical entities. Thus, automatic systems for the identification of citations of allelic variants of genes in biomedical texts are required. Results: Our group has previously reported the development of OSIRIS, a system aimed at the retrieval of literature about allelic variants of genes http://ibi.imim.es/osirisform.html. Here we describe the development of a new version of OSIRIS (OSIRISv1.2, http://ibi.imim.es/OSIRISv1.2.html webcite) which incorporates a new entity recognition module and is built on top of a local mirror of the MEDLINE collection and HgenetInfoDB: a database that collects data on human gene sequence variations. The new entity recognition module is based on a pattern-based search algorithm for the identification of variation terms in the texts and their mapping to dbSNP identifiers. The performance of OSIRISv1.2 was evaluated on a manually annotated corpus, resulting in 99% precision, 82% recall, and an F-score of 0.89. As an example, the application of the system for collecting literature citations for the allelic variants of genes related to the diseases intracranial aneurysm and breast cancer is presented. Conclusion: OSIRISv1.2 can be used to link literature references to dbSNP database entries with high accuracy, and therefore is suitable for collecting current knowledge on gene sequence variations and supporting the functional annotation of variation databases. The application of OSIRISv1.2 in combination with controlled vocabularies like MeSH provides a way to identify associations of biomedical interest, such as those that relate SNPs with diseases.

The Multiscenario Multienvironment BioSecure Multimodal Database (BMDB)

A new multimodal biometric database designed and acquired within the framework of the European BioSecure Network of Excellence is presented. It is comprised of more than 600 individuals acquired simultaneously in three scenarios: 1) over the Internet, 2) in an office environment with desktop PC, and 3) in indoor/outdoor environments with mobile portable hardware. The three scenarios include a common part of audio/video data. Also, signature and fingerprint data have been acquired both with desktop PC and mobile portable hardware. Additionally, hand and iris data were acquired in the second scenario using desktop PC. Acquisition has been conducted by 11 European institutions. Additional features of the BioSecure Multimodal Database (BMDB) are: two acquisitionsessions, several sensors in certain modalities, balanced gender and age distributions, multimodal realistic scenarios with simple and quick tasks per modality, cross-European diversity, availability of demographic data, and compatibility with other multimodal databases. The novel acquisition conditions of the BMDB allow us to perform new challenging research and evaluation of eithermonomodal or multimodal biometric systems, as in the recent BioSecure Multimodal Evaluation campaign. A description of this campaign including baseline results of individual modalities from the new database is also given. The database is expected to beavailable for research purposes through the BioSecure Association during 2008.

Study of common database feeding with results coming from different analytical methods in the framework of illicit drugs chemical profiling

Analytical results harmonisation is investigated in this study to provide an alternative to the restrictive approach of analytical methods harmonisation which is recommended nowadays for making possible the exchange of information and then for supporting the fight against illicit drugs trafficking. Indeed, the main goal of this study is to demonstrate that a common database can be fed by a range of different analytical methods, whatever the differences in levels of analytical parameters between these latter ones. For this purpose, a methodology making possible the estimation and even the optimisation of results similarity coming from different analytical methods was then developed. In particular, the possibility to introduce chemical profiles obtained with Fast GC-FID in a GC-MS database is studied in this paper. By the use of the methodology, the similarity of results coming from different analytical methods can be objectively assessed and the utility in practice of database sharing by these methods can be evaluated, depending on profiling purposes (evidential vs. operational perspective tool). This methodology can be regarded as a relevant approach for database feeding by different analytical methods and puts in doubt the necessity to analyse all illicit drugs seizures in one single laboratory or to implement analytical methods harmonisation in each participating laboratory.

Early Christian School Texts on Papyri: the database

Database of papyrus school texts which may be identified as Christian on the basis of the presence of some internal indicator: Christian symbols, textual content originating from the Bible or of a clearly Christian origin proposed as a copying exercise, or Christian contents not part of the exercise itself, such as prayers or invocations.

Do pornographic websites influence boys' sexual behavior?

Purpose: To compare the sexual behavior of adolescent males who do and do not watch pornographic websites. Methods: This study was presented as a school survey. Data were drawn from the 2002 Swiss Multicenter Adolescent Survey on Health (SMASH02) database, a survey including 7,548 adolescents age 16-20. The setting was post-mandatory schools in Switzerland. A total of 2,891 male students who connected to the internet in the last 30 days were enrolled and distributed into two groups: boys who deliberately watched pornographic websites in the last 30 days (n ¼ 942; 33%) and boys who did not (n ¼ 1,949; 67%). Socio-demographic characteristics; frequency of connection to the internet; sexual behavior parameters (having a girlfriend and if yes, for more or less than 6 months; having had sexual intercourse; age at first sexual intercourse; use of a condom at last sexual intercourse; number of sexual partners; having made a partner pregnant). Results: A logistic regression was performed using STATA 9.2. The only significant socio-demographic variable was having a low socioeconomic status (adjusted odds ratio [AOR] 1.66); no difference was found for age and academic track between the two groups. Boys who watch pornographic websites were also significantly more likely to connect frequently to the internet (one day a week: AOR 1.75; several days a week: AOR 2.36; every day: AOR 3.11), to have had sexual intercourse (AOR 2.06), and to have had their first sexual intercourse before age 15 (AOR 1.48). The stability of the relationship with their girlfriend did not appear to have any influence on the search for pornography on the internet. Conclusions: About one third of boys in our sample report having accessed pornographic websites in the last 30 days, a proportion similar to other studies. Watching such websites increases with the frequency of connection to the internet and seems to be correlated with an earlier sexual activity debut among adolescent males. However, having had first sexual intercourse before age 15 is the only sexual risk behavior that seems to be increased when watching pornographic websites among boys. Further studies should address the causality of this correlation and the factors influencing the search for pornography on the web among boys, in order to explore some new ways of prevention about sexual risk behaviors. Sources of Support: The SMASH02 survey was carried out with the financial support of the Swiss Federal Office of Public Health and the participating cantons.

International nursing : cultivating a culture of empowerment

International nursing has been a growing phenomenon throughout the globe. International nurses have been found to be an asset to healthcare organizations and an important part of the health care team. However, growing concern for the plight of international nurses facing obstacles such as professional stagnation and exploitation has spurred the development of strategies to mitigate and ameliorate the experiences of nurses working abroad. In this respect, the purpose of this study was to explore the management-influenced factors and the nurse team-influenced factors that promote the empowerment of the international nurse in the health care setting. The methodology used in this study was a systemic review. After a rigorous search for relevant empirical studies using OVID database, eight empirical research studies were selected using systematic review methodology to collect, analyze and synthesize data. The selected eight empirical studies were then subjected to a content analysis. The results suggested that the empowerment of an international nurse is inseparable from the empowerment of the health care organization. Based on the findings in this study, strategies to promote international nurses were found to mirror strategies evidenced to empower the nursing organization. Some of the management-influenced factors which were found to facilitate empowerment included a diversity rich work culture, transformational leadership at the management level, and a responsibility to foster the values of the organization. The team-influenced factors which were found to contribute to the empowerment of the international nurse included a united mutually-interdependent nurse team, shared accountability among the members of the nurse team, and the building of trust in work relationships. To conlude, this study indicates that efforts to empower international nurses without considering the work culture and the organization as a whole are futile because empowerment cannot take place in an environment that lacks antecedent conditions. Strategies to empower the international nurse should not focus on the deficits and special needs of the international nurse, but should focus on the similarities and commonalities of the nursing body. Empowerment of the international nurse mean open honest communication, supportive work environment, and a firm policy to quell disruptive elements that threaten the organization's values, mission, and philosophy of care.

Reverse transcription quantitative real-time polymerase chain reaction reference genes in the spared nerve injury model of neuropathic pain: validation and literature search.

BACKGROUND: The reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) is a widely used, highly sensitive laboratory technique to rapidly and easily detect, identify and quantify gene expression. Reliable RT-qPCR data necessitates accurate normalization with validated control genes (reference genes) whose expression is constant in all studied conditions. This stability has to be demonstrated.We performed a literature search for studies using quantitative or semi-quantitative PCR in the rat spared nerve injury (SNI) model of neuropathic pain to verify whether any reference genes had previously been validated. We then analyzed the stability over time of 7 commonly used reference genes in the nervous system - specifically in the spinal cord dorsal horn and the dorsal root ganglion (DRG). These were: Actin beta (Actb), Glyceraldehyde-3-phosphate dehydrogenase (GAPDH), ribosomal proteins 18S (18S), L13a (RPL13a) and L29 (RPL29), hypoxanthine phosphoribosyltransferase 1 (HPRT1) and hydroxymethylbilane synthase (HMBS). We compared the candidate genes and established a stability ranking using the geNorm algorithm. Finally, we assessed the number of reference genes necessary for accurate normalization in this neuropathic pain model. RESULTS: We found GAPDH, HMBS, Actb, HPRT1 and 18S cited as reference genes in literature on studies using the SNI model. Only HPRT1 and 18S had been once previously demonstrated as stable in RT-qPCR arrays. All the genes tested in this study, using the geNorm algorithm, presented gene stability values (M-value) acceptable enough for them to qualify as potential reference genes in both DRG and spinal cord. Using the coefficient of variation, 18S failed the 50% cut-off with a value of 61% in the DRG. The two most stable genes in the dorsal horn were RPL29 and RPL13a; in the DRG they were HPRT1 and Actb. Using a 0.15 cut-off for pairwise variations we found that any pair of stable reference gene was sufficient for the normalization process. CONCLUSIONS: In the rat SNI model, we validated and ranked Actb, RPL29, RPL13a, HMBS, GAPDH, HPRT1 and 18S as good reference genes in the spinal cord. In the DRG, 18S did not fulfill stability criteria. The combination of any two stable reference genes was sufficient to provide an accurate normalization.

The Alps Vegetation Database - a geo-referenced community-level archive of all terrestrial plants occurring in the Alps.

Mountain ranges are biodiversity hotspots worldwide and provide refuge to many organisms under contemporary climate change. Gathering field information on mountain biodiversity over time is of primary importance to understand the response of biotic communities to climate changes. For plants, several long-term observation sites and networks of mountain biodiversity are emerging worldwide to gather field data and monitor altitudinal range shifts and community composition changes under contemporary climate change. Most of these monitoring sites, however, focus on alpine ecosystems and mountain summits, such as the global observation research initiative in alpine environments (GLORIA). Here we describe the Alps Vegetation Database, a comprehensive community level archive (GIVD ID EU-00-014) which aims at compiling all available geo-referenced vegetation plots from lowland forests to alpine grasslands across the greatest mountain range in Europe: the Alps. This research initiative was funded between 2008 and 2011 by the Danish Council for Independent Research and was part of a larger project to compare cross-scale plant community structure between the Alps and the Scandes. The Alps Vegetation Database currently harbours 35,731 geo-referenced vegetation plots and 5,023 valid taxa across Mediterranean, temperate and alpine environments. The data are mainly used by the main contributors of the Alps Vegetation Database in an ecoinformatics approach to test hypotheses related to plant macroecology and biogeography, but external proposals for joint collaborations are welcome.

Computerized advice on drug dosage to improve prescribing practice.

BACKGROUND: Maintaining therapeutic concentrations of drugs with a narrow therapeutic window is a complex task. Several computer systems have been designed to help doctors determine optimum drug dosage. Significant improvements in health care could be achieved if computer advice improved health outcomes and could be implemented in routine practice in a cost effective fashion. This is an updated version of an earlier Cochrane systematic review, by Walton et al, published in 2001. OBJECTIVES: To assess whether computerised advice on drug dosage has beneficial effects on the process or outcome of health care. SEARCH STRATEGY: We searched the Cochrane Effective Practice and Organisation of Care Group specialized register (June 1996 to December 2006), MEDLINE (1966 to December 2006), EMBASE (1980 to December 2006), hand searched the journal Therapeutic Drug Monitoring (1979 to March 2007) and the Journal of the American Medical Informatics Association (1996 to March 2007) as well as reference lists from primary articles. SELECTION CRITERIA: Randomized controlled trials, controlled trials, controlled before and after studies and interrupted time series analyses of computerized advice on drug dosage were included. The participants were health professionals responsible for patient care. The outcomes were: any objectively measured change in the behaviour of the health care provider (such as changes in the dose of drug used); any change in the health of patients resulting from computerized advice (such as adverse reactions to drugs). DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted data and assessed study quality. MAIN RESULTS: Twenty-six comparisons (23 articles) were included (as compared to fifteen comparisons in the original review) including a wide range of drugs in inpatient and outpatient settings. Interventions usually targeted doctors although some studies attempted to influence prescriptions by pharmacists and nurses. Although all studies used reliable outcome measures, their quality was generally low. Computerized advice for drug dosage gave significant benefits by:1.increasing the initial dose (standardised mean difference 1.12, 95% CI 0.33 to 1.92)2.increasing serum concentrations (standradised mean difference 1.12, 95% CI 0.43 to 1.82)3.reducing the time to therapeutic stabilisation (standardised mean difference -0.55, 95%CI -1.03 to -0.08)4.reducing the risk of toxic drug level (rate ratio 0.45, 95% CI 0.30 to 0.70)5.reducing the length of hospital stay (standardised mean difference -0.35, 95% CI -0.52 to -0.17). AUTHORS' CONCLUSIONS: This review suggests that computerized advice for drug dosage has some benefits: it increased the initial dose of drug, increased serum drug concentrations and led to a more rapid therapeutic control. It also reduced the risk of toxic drug levels and the length of time spent in the hospital. However, it had no effect on adverse reactions. In addition, there was no evidence to suggest that some decision support technical features (such as its integration into a computer physician order entry system) or aspects of organization of care (such as the setting) could optimise the effect of computerised advice.

Clinical reasoning in undergraduate nursing education: a scoping review

Abstract OBJECTIVE This study aimed at analyzing the current state of knowledge on clinical reasoning in undergraduate nursing education. METHODS A systematic scoping review through a search strategy applied to the MEDLINE database, and an analysis of the material recovered by extracting data done by two independent reviewers. The extracted data were analyzed and synthesized in a narrative manner. RESULTS From the 1380 citations retrieved in the search, 23 were kept for review and their contents were summarized into five categories: 1) the experience of developing critical thinking/clinical reasoning/decision-making process; 2) teaching strategies related to the development of critical thinking/clinical reasoning/decision-making process; 3) measurement of variables related to the critical thinking/clinical reasoning/decision-making process; 4) relationship of variables involved in the critical thinking/clinical reasoning/decision-making process; and 5) theoretical development models of critical thinking/clinical reasoning/decision-making process for students. CONCLUSION The biggest challenge for developing knowledge on teaching clinical reasoning seems to be finding consistency between theoretical perspectives on the development of clinical reasoning and methodologies, methods, and procedures in research initiatives in this field.